886C Poster - 14. Neural circuits and behavior
Saturday April 09, 1:30 PM - 3:30 PM

Authors:
Shanzeh Sayied ¹; Kim Madhwani ¹; Caley Hogan ²; Kate O'Connor-Giles ^{1, 3}

Affiliations:
1) Brown University; 2) University of Wisconsin-Madison; 3) Carney Institute for Brain Science

Keywords:
f. learning/memory; k. feeding behavior

Regulation of neuronal gene expression is crucial for proper neuronal development and function and occurs at numerous steps, from DNA methylation to protein degradation. Transfer RNAs (tRNAs) are emerging as an important point of regulation. tRNAs are heavily post-transcriptionally modified to regulate tRNA structure and stability and strengthen anticodon-codon interactions. Recently, variants in tRNA-modifying enzymes have been associated with multiple neurological disorders. In particular, mutations in ALKBH8, which encodes a highly conserved tRNA methyltransferase, have recently been linked to intellectual disability in four families. While ALKBH8 has been studied in the context of oxidative stress, its role in the nervous system remains unknown. Due to its role in translation and link to intellectual disability, we hypothesized that ALKBH8 may promote the translation-dependent processes of learning and memory. We generated ALKBH8 null mutants and analyzed sensory memory using a taste aversion assay. The taste aversion assay measures a reduction in the sucrose-induced proboscis extension reflex (PER) after starved female flies learn to associate sucrose with the aversive tastant quinine. Our findings reveal a deficit in the formation of aversive taste memories in ALKBH8 null mutants. These results indicate learning deficits consistent with intellectual disability in humans and establish Drosophila as a model for understanding the underlying mechanisms of ALKBH8-associated intellectual disability.